Reduction in Hepatocyte Growth Factor Serum Levels is Associated with Improved Prognosis in Advanced Lung Adenocarcinoma Patients Treated with Afatinib: a Phase II Trial
Reduction in Hepatocyte Growth Factor Serum Levels is Associated with Improved Prognosis in Advanced Lung Adenocarcinoma Patients Treated with Afatinib: a Phase II Trial
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DOI：
10.1007/s11523-016-0425-x
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发表时间：
2016-10-01
影响因子：
5.4
通讯作者：
Astudillo-de la Vega, Horacio
中科院分区：
文献类型：
--
作者：
Arrieta, Oscar;Cruz-Rico, Graciela;Astudillo-de la Vega, Horacio
C-met及其配体肝细胞生长因子（HGF）与EGFR TKI的耐药机制有关。在接受阿法替尼治疗的NSCLC患者中，将HGF作为缓解的临床标志物进行评价。66例IIIB/IV期肺腺癌患者进展至任何线化疗，接受阿法替尼40 mg/天治疗。通过RT-PCR评估突变EGFR和HER 2状态。通过FISH评估HER 2扩增。治疗前和治疗后2个月分别用ELISA法测定血清HGF含量。用客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）评估HGF水平。该试验在ClinicalTrials.gov上注册：NCT 01542437。50例患者（75%）为EGFR突变阳性。59%的患者和78%的EGFR突变患者达到缓解。所有患者和EGFR突变患者的中位PFS分别为10个月[95% CI 6.8-13.1]和14.5个月[10.9-18.9]。所有患者和EGFR突变患者的中位OS分别为22.8 [17.5-28.1]和32.4个月[18.3-46.6]。血清HGF水平降低的患者的ORR（75% vs 44%; p = 0. 011）、PFS（15. 1 [2. 9 - 27. 3] vs 6. 5个月[3. 9 - 9. 1]; p = 0. 005）和OS（NR vs 14. 5个月[7. 8 - 21. 3] p = 0. 007）改善。在所有患者和EGFR突变患者中，血清HGF水平降低是与PFS（HR 0.40; p = 0.021）和OS（HR 0.31; p = 0.006）延长相关的独立因素。在接受阿法替尼治疗的患者中，血清HGF水平降低与结局改善相关。这些结果表明，HGF可能具有作为对EGFR-TKI的抗性机制的作用。HGF可能代表一个潜在的治疗靶点，以预防或逆转耐药，特别是在EGFR突变的患者。
C-met and its ligand, hepatocyte growth factor (HGF) have been associated with the resistance mechanism of EGFR-TKIs. HGF was evaluated as a clinical-marker of response in NSCLC patients treated with afatinib.Sixty-six patients with stage IIIB/IV lung adenocarcinoma and progression to any-line chemotherapy received afatinib 40 mg/day. Mutational EGFR and HER2 status were assessed by RT-PCR. HER2 amplification was evaluated by FISH. Serum HGF content was measured by ELISA before and 2 months after the start of treatment. HGF levels were assessed with the objective response rate (ORR), progression-free-survival (PFS), and overall survival (OS). This trial was registered on ClinicalTrials.gov: NCT01542437.Fifty patients (75 %) were EGFR mutation positive. Response was achieved in 59 % of all patients and 78 % of EGFR mutated patients. Median PFS was 10 [95 % CI 6.8-13.1] and 14.5 months [10.9-18.9] for all and EGFR mutated patients, respectively. Median OS was 22.8 [17.5-28.1] and 32.4 months [18.3-46.6] for all and EGFR mutated patients, respectively. Patients with reduced serum HGF levels had improved ORR (75 % vs 44 %; p = 0.011), PFS (15.1 [2.9-27.3] vs 6.5 months [3.9-9.1]; p = 0.005) and OS (NR vs 14.5 months [7.8 - 21.3] p = 0.007). A reduction in serum HGF levels was an independent factor associated with longer PFS (HR 0.40; p = 0.021) and OS (HR 0.31; p = 0.006) in all and EGFR mutated patients.A reduction in serum HGF levels was associated with improved outcomes in patients treated with afatinib. These results suggest HGF might have a role as a mechanism of resistance to EGFR-TKIs. HGF could represent a potential therapeutic target to prevent or reverse resistance particularly in EGFR mutated patients.